High-sensitivity Troponin I Predicts Galectin-3 in Chronic Kidney Disease Patients

International Urology and Nephrology - Plasma galectin-3 (pG3) regulates inflammation. B-type natriuretic peptide (BNP), high-sensitivity Troponin I (hsTnI), and pG3 concentrations are elevated in...     

Tailored internal limiting membrane flap technique for primary macular hole

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate the outcomes of primary full-thickness macular hole (MH) after surgical intervention with tailored internal...     

cGMP: transition from bench to bedside: a report of the 6th International Conference on cGMP Generators,Effectors and Therapeutic Implications

Essential physiological homeostatic processes such as vascular tone, fluid balance, cardiorenal function, and sensory processes are regulated by the second messenger cyclic guanosine 3′, 5′-monophosphate (cGMP). Dysregulation of cGMP-dependent pathways plays an important role in cardiovascular diseases such as hypertension, pulmonary hypertension, heart failure, or erectile dysfunction. Thus, the cGMP pathway consisting of the cGMP-generating guanylyl cyclases, protein kinases, and phosphodiesterases (PDE) has evolved to an important drug target and is the focus of a wide variety of research fields ranging from unraveling mechanisms on the molecular level to understanding the regulation of physiological and pathophysiological processes by cGMP. Based on the results from basic and preclinical research, therapeutic drugs have been developed which modulate the cGMP pathway and are investigated in clinical trials. Riociguat, a nitric oxide (NO)-independent soluble guanylyl cyclase stimulator; recombinant B-type natriuretic peptide (BNP); or recombinant atrial natriuretic peptide (ANP) and PDE5 inhibitors are cGMP-modulating drugs that are already available for the treatment of pulmonary hypertension, acute heart failure, and erectile dysfunction, respectively. The latest results from basic to clinical research on cGMP were presented on the 6th International Conference on cGMP in Erfurt, Germany, and are summarized in this article.     

Citrulline levels following proximal versus distal small bowel resection

Purpose

Citrulline, a nonprotein amino acid synthesized by enterocytes, is a biomarker of bowel length and the capacity to wean from parenteral nutrition. However, the potentially variant effect of jejunal versus ileal excision on plasma citrulline concentration [CIT] has not been studied. This investigation compared serial serum [CIT] and mucosal adaptive potential after proximal versus distal small bowel resection.

Methods

Enterally fed Sprague-Dawley rats underwent sham operation or 50% small bowel resection, either proximal (PR) or distal (DR). [CIT] was measured at operation and weekly for 8 weeks. At necropsy, histologic features reflecting bowel adaptation were evaluated.

Results

By weeks 6–7, [CIT] in both resection groups significantly decreased from baseline (P < 0.05) and was significantly lower than the concentration in sham animals (P < 0.05). There was no difference in [CIT] between PR and DR at any point. Villus height and crypt density were higher in the PR than in the DR group (P ≤ 0.02).

Conclusion

[CIT] effectively differentiates animals undergoing major bowel resection from those with preserved intestinal length. The region of intestinal resection was not a determinant of [CIT]. The remaining bowel in the PR group demonstrated greater adaptive potential histologically. [CIT] is a robust biomarker for intestinal length, irrespective of location of small intestine lost.     

Urgency to treat patients with chronic hepatitis C in Asia

Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)‐based therapy than non‐Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN‐based therapies. Superior virologic outcomes have been observed with different classes of direct‐acting antivirals (DAAs) alone or in combination, and several all‐oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world context, particularly in Asia. Furthermore, IFN‐free treatment may not be accessible for many patients in the region, and IFN‐based regimens remain an option in some countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost‐effectiveness of IFN‐free regimens. The evolution of potent treatments makes HCV eradication a possibility that should be available to all patients. However, access to these therapies in Asian countries has been slow, primarily because of economic barriers that continue to present a hurdle to optimal treatment.     

A critical role of TRAIL expressed on cotransplanted hepatic stellate cells in prevention of islet allograft rejection

Hepatic stellate cells (HSCs) have demonstrated a strong T‐cell inhibitory activity. In a mouse islet transplantation model, cotransplanted HSCs can protect islet allografts from rejection. The involved mechanism is not fully understood. We showed in this study that expression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), an important apoptosis‐inducing ligand, on HSCs was crucial in protection of islet allografts, since HSCs derived from TRAIL knockout mice demonstrated less inhibitory activity towards T‐cell proliferative responses, and substantially lost their capacity in protecting cotransplanted islet allografts from rejection, suggesting that TRAIL‐mediated T cell apoptotic death is important in HSC‐delivered immune regulation activity. © 2009 Wiley‐Liss, Inc. Microsurgery 2010.     

Impaired gist memory in patients with temporal lobe epilepsy and hippocampal sclerosis

Purpose: Temporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memory functions. We aimed to examine the effect of restricted hippocampal lesions on gist memory function in patients with TLE. Methods: Forty‐five patients with TLE and HS (16 left, 15 right, and 14 bilateral lesions) and 22 control subjects were recruited. Patients with magnetic resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal lesions were excluded. All participants performed a gist‐based recognition task following the Deese‐Roediger‐McDermott paradigm and were tested for verbal IQ and memory functions. We conducted hippocampal volumetry on MRI of all the participants. Results: Patients showed multidomain memory impairments. Gist memory was impaired in patients with bilateral HS and probably in patients with right HS. Hippocampal volumetry supported such findings that total volume of hippocampi and volume of right hippocampus correlated positively with gist memory function. Discussion: HS has a dose effect and a probable right dominance effect on gist memory; good item memory supports gist memory performance; and a disproportionate deficit was noted in tasks with high relational demand but not in tasks with simple association. We should develop memory skills for patients with TLE by enhancing performance of gist memory related to simple association task.     

Down-regulation of von Hippel-Lindau protein in N-nitroso compound-induced rat non-clear cell renal tumors

Non-clear cell rat kidney tumors, inducible by N-nitroso compounds but lacking mutations in the von Hippel--Lindau (VHL) coding sequence, were examined for other VHL alterations. Neither mutations nor DNA methylation was detected in a putative promoter region. By immunohistochemistry, however, VHL protein level was evidently reduced in six of the eight eosinophilic renal epithelial tumors and in all the ten nephroblastomas. Immunoblotting of normal kidney detected two VHL proteins of 20 and 22kDa in a 16-day-old fetal rat but only 20kDa protein in an adult rat. This is the first demonstration of VHL alteration at the protein level.     

Induction of differentiation in rat C6 glioma cells with Saikosaponins

The effects of saikosaponins (a, b(1), b(2), c, d), isolated from Bupleurum Radix, on the induction of differentiation in rat C6 glioma cells were studied. Saikosaponins a and d were shown to inhibit cell proliferation and alter cell morphology. In addition to cytostasis, the enzymatic activities of glutamine synthetase (GS) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) were also noticeably increased after treatment with saikosaponin a. Nevertheless, saikosaponin d only showed an increase of GS activity, no significant changes in CNP activity were found. These results suggest that saikosaponin a can induce the differentiation of C6 glioma cells into astrocytes and/or oligodendrocytes, but saikosaponin d can only induce the differentiation of C6 glioma cells into astrocytes.